..These findings provide the first evidence for the rapid emergence of clinical resistance to a novel class of HIV-1 entry inhibitors and may be relevant to future treatment strategies involving these agents...

..Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease...

Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target

..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival...

..Results suggest the hypothesis that targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early AD...

..These findings are consistent with the idea that N-terminal fragments of huntingtin with a repeat expansion are toxic to neurons, and that N-terminal fragments are prone to form both intranuclear inclusions and neuritic aggregates...

Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas

..The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-beta units with their hydrophobic faces juxtaposed...

Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia

..Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease...

Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report

James A R NicollDivision of Clinical Neurosciences, University of Southampton, Southampton, UKNat Med 9:448-52. 2003

..The T-lymphocyte meningoencephalitis is likely to correspond to the side effect seen in some other patients who received AN-1792 (refs. 7-9)...

Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease

..Our results are consistent with previous observations that Aβ40 and Aβ42 self-assemble via different pathways and provide a candidate in the Aβ42 dodecamer for the primary toxic species in Alzheimer's disease...

..Our results indicate that mutations in PS1 that manifest clinically cause a gain of function and that inhibition of PS1 activity is a potential target for anti-amyloidogenic therapy in Alzheimer's disease...

Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio

..The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets...

Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease

..These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials...

..The annular anti-protofibril antibody also recognizes heptameric alpha-hemolysin pores, but not monomers, suggesting that the antibody recognizes an epitope that is specific for a beta barrel structural motif...

Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis

..However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required...

..This protection appears to involve activating multiple prosurvival kinases. This finding may represent a new therapeutic potential for this class of drug currently undergoing clinical trials in the treatment of type 2 diabetes...

..The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients...

..To explore if soluble amyloid precursor proteins (sAPP) in CSF improve the identification of patients with incipient Alzheimer disease (AD) in a group of patients with mild cognitive impairment (MCI)...

..1-1 microM. Although the mechanism by which Cur and RA inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD...

Structural basis for coreceptor selectivity by the HIV type 1 V3 loop

Timothy CardozoDepartment of Pharmacology and New York University School of Medicine, New York, NY 10016, USAAIDS Res Hum Retroviruses 23:415-26. 2007

..The results have additional implications for the design of HIV therapeutics, vaccines, and strategies for monitoring disease progression...

..According to numerical simulation based on the successive reaction kinetics, the induction period exists. These results strongly suggest that Abeta is generated through the stepwise processing of betaCTF by gamma-secretase...

..We conclude therefore that both IL-17A and IL-17F, while prominently expressed by an encephalitogenic T cell population, may only marginally contribute to the development of autoimmune CNS disease...

..At default thresholds, OMSSA matches more spectra from a standard protein cocktail than a comparable algorithm. OMSSA is designed to be faster than published algorithms in searching large MS/MS datasets...

Maria E BambergerAlzheimer Research Laboratory, Program in Cell Biology and Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USAJ Neurosci 23:2665-74. 2003

..Identification of the cell surface molecules that interact with Abeta fibrils and mediate their activation of intracellular signaling cascades represents a potential intervention point in the treatment of Alzheimer's disease...

..These studies identify an important mechanism through which microglial cells participate in the maintenance of Abeta homeostasis, through their capacity to constitutively clear sAbeta peptides from the brain...

..The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development...

..In this review, we will focus on the recent findings related to the ACE2-Ang(1-7)-Mas axis and, in particular, on its putative role as an ACE-Ang II-AT(1) receptor counter-regulatory axis within the RAS...

RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain

..Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains...

..Although peripheral administration of m266 to PDAPP mice markedly reduces A beta deposition, m266 did not bind to A beta deposits in the brain. Thus, m266 appears to reduce brain A beta burden by altering CNS and plasma A beta clearance...

..These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II...

..The continuing flow of new details into our understanding of the biology of MHC class I and class II antigen presentation builds a system involving several cell biological processes, which is discussed in this Review...

Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap

..function and normal cross-linking which would lead to proteolysis and self-immunization with auto-antigenic peptide fragments. The objective of this particular proposal is to determine peroxidasin's role in the pathogenesis of ..

..overall hypothesis is that loss of XPNPEP3 function increases the degradation of mitochondrial proteins to peptide fragments, which are transported into the cytosol where they upregulate TOR activity...

..and biophysical techniques will be used to map the binding interaction of CN and PERK and to generate the peptide fragments. Primary cultures of astrocytes will be used to test the efficacy of these molecular interventions in vivo...

..hypothesis for AD initiation and progression is the amyloid cascade hypothesis, which proposes that Ass peptide fragments of human APP are necessary and sufficient to initiate and to drive all downstream pathologies typical of AD ..

..Although there are many informative high resolution structures of calmodulin bound to peptide fragments derived from ion channels, the location of calmodulin on functioning channels and the calcium-induced ..

..will be carried out by comparing antibody binding to denatured allergens, chemically modified allergens and peptide fragments. The aim will be to determine the repertoire of B cell epitopes, whether they are sequential or topographic ..

..as macrophages and B-lymphocytes and are processed within these cells by unfolding and proteolysis to short peptide fragments. These fragments are then displayed on the cell surface, bound to MHC class II molecules...

The processing of soluble protein antigens to peptide fragments by antigen-presenting cells (APCs) is usually required for the stimulation of CD4+ T cells. The mechanism and location whereby APCs produce antigenic peptides are unclear...

..taken back up by neurons following their release but are metabolized in the extracellular space into smaller peptide fragments. These fragments can directly affect the cells in the extracellular space in the surrounding area, pass ..

..Granins also function as pro-hormones, giving rise by proteolytic processing to a large array of peptide fragments for which diverse autocrine, paracrine, and endocrine activities have been demonstrated in vitro, ex vivo ..

..used are: inhibition, reduction and alkylation, G-75 Sephadex separation of the peptides, sequencing of the peptide fragments formed as a result of O-alkylation of amide linkages, chemical modification of intact C-chain to increase ..

..Recently, investigators have identified a functional defect in endogenous presentation of self-peptide fragments in the groove of major histocompatibility complex (MHC) class I molecules in patients with autoimmune ..

..It is now known that cytotoxic T lymphocytes (CTL) detect target cells for killing by recognizing short peptide fragments of endogenous proteins which are presented to them by class I MHC molecules on the surface of the target ..